Summary of Aβ segmental polymorphic oligomeric models and Simulation Conditions.

<p>Summary of Aβ segmental polymorphic oligomeric models and Simulation Conditions.</p

The structural changes in each model, from the trajectory with the largest average root-mean-square-deviations, at the end of 300 ns of molecular dynamics in explicit solvent (water molecules omitted for clarity).

<p>A) Single layer conformation of human amylin, (B) single layer conformation of rat amylin, (C) single layer conformation of human-rat complex, (D) Double layer conformation of human amylin with CC interface (E) Double layer conformation of rat amylin with CC interface, (F) Double layer conformation of rat and human amylin mixtures with CC interface, (G) Double layer conformation of rat amylin with NN interface and (H) Double layer conformation of rat–human amylin complex with NN interface. The segments that are colored yellow are the N terminal segments (residue 8–17) and the C terminal segment (residue 28–37). Different colors are applied for the rat (red) and human amylin (green). The initial structures are depicted in blue. Root-mean-square-deviation values calculated for each peptide with respect to the start configurations are included in parentheses.</p

MM-PBSA free energy calculations and different Components of the binding free energy.

<p>The data are averages of two independent 40 ns simulation with the corresponding standard deviations. All values are in kcal/mol. The polar term is the sum of Coulomb interaction energy (E_elec) and polar contribution to the solvation free energy (E_PB). The nonpolar term consists of takes the van der Waals interaction energies (E_vdW) and the nonpolar contribution to the solvation free energy (E_SA).</p

Percentage of hydrogen bonds as a function time with respect to the energy minimized structure of Aβ segmental polymorphic models.

<p>Red, 16–21P; green, 16–21AP; blue, 27–32; pink, 35–42; cyano, 30–42.</p

Root Mean Square Deviation (RMSD) and Radius gyration (Rg) for the Aβ segmental polymorphism models.

<p>Variation of the C_α atom root mean square deviation (RMSD) with respect the energy minimized structure of the five segmental polymorphic models of Aβ. The of each model was calculated using two independent trajectories (A). Radius of gyration as a function of time for each structures during the 50 ns MD simulations (B). Red, 16–21P; pink, 16–21AP; blue, 27–32; green, 35–42; yellow, 30–42.</p

Average number of main chain and side chain hydrogen bonds.

<p>(A) Total number of main chain hydrogen bonds; (B) total number of side chain hydrogen bonds. Legend: (I) Single layer conformation of rat amylin, (II) single layer conformation of human amylin, (III) single layer conformation of human-rat complex, (IV) Double layer conformation of rat amylin with CC interface (V) Double layer conformation of human amylin with CC interface, (VI) Double layer conformation of rat and human amylin mixtures with CC interface, (VII) Double layer conformation of human amylin with NN interface and (VIII) Double layer conformation of rat–human amylin complex with NN interface.</p

Single layer and double layer decamer models and simulations conditions.

<p>SL marks single layer decamers and DL double layer decamers. The symbol * marks the mixed rat-human amylin complexes, where the first five strands are from the human amylin sequences and the last five strands are form rat amylin sequence. NN strands for N-terminal-N-terminal interface and CC strands for C-terminal-C-terminal interface.</p

Secondary structure variation plot for each of the Aβ segmental polymorphism models.

<p>(A) Aβ₁₆₋₂₁P, (B) Aβ₁₆₋₂₁AP (C) Aβ₂₇₋₃₂, (D) Aβ₃₅₋₄₂ and (E) Aβ₁₃₀₋₄₂ interfaces. The secondary structure color codes: red-β-sheet, green-bend, yellow-turn, blue -α-helix, coil-white. Where L stands for the peptide layers number and C stands for the peptide chain number.</p

Average inter-sheets salt–bridge distance (Lys_n¹⁶/Glu_n²²) along simulation for 16–21P and 16–21AP.

<p>A) 16–21P and (B) 16–21AP. The results are the average of two independent simulation of each system. Red, ₁K¹⁶-₁E²²; pink, ₂K¹⁶-₂E²²; blue, ₃K¹⁶-₃E²²; green_{, 4}K¹⁶-₄E²²; yellow, ₅K¹⁶-₅E²². Red, 16–21P; green, 16–21AP; blue, 27–32; pink, 35–42; cyano, 30–42.</p

Face to face contact distances of CC interface double layers of human amylin, rat amylin and their cross-seeded oligomers (human amylin|rat amylin).

<p>Hydrophobic contact of C_α−C_α distances (Å) between the residues L₂₇/G₃₃, S₂₉/N₃₁, N₃₁/S₂₉ and G₃₃/L₂₇ of human amylin and L₂₇/G₃₃, P₂₉/N₃₁, N₃₁/P₂₉ and G₃₃/L₂₇ of rat amylin and their hetero-assembly. *Sh = sheet and St = strand. Values are shown after excluding the first and the last chain of the each of the β-hairpin structures.</p